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Correlation between augmenter of liver regeneration and IFN-¦Ã expression in graft after rat orthotopic liver transplantation
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文摘

Background

Previous data suggested that augmenter of liver regeneration (ALR) has immunomodulation function by suppressing liver-resident NK cell activity and reducing IFN-¦Ã expression in human liver diseases. The correlation between ALR and IFN-¦Ã expression in graft after rat orthotopic liver transplantation remains uncertain.

Methods

A Lewis-to-BN (allograft group) and BN-to-BN (isograft group) rat liver transplantation model was used to investigate the ALR and IFN-¦Ã expression in liver graft. Graft recipients were sacrificed at days 1, 3, 5, and 7 posttransplantation. The histopathologic changes of grafts were observed under light microscope and the intragraft expression of ALR and IFN-¦Ã mRNA and protein was determined by real-time PCR and immunohistochemistry staining, respectively. Correlation between ALR and IFN-¦Ã expression in graft was evaluated by Spearman rank correlation analysis.

Results

The light microscope inspection revealed severe acute rejection in the allograft group but not in the isograft group at day 7 after liver transplantation. The intragraft ALR showed slight protein expression at day 1 after liver transplantation in both groups and it was significantly increased at days 3, 5, and 7 (P < 0.05). There was no significant difference in ALR mRNA expression between the allograft group and isograft group at day 1 (1.09 ¡À 0.12 and 1.13 ¡À 0.10, respectively; P > 0.05, n = 3). The ALR mRNA level was slightly reduced at day 3 in both groups compared with that at day 1 (0.81 ¡À 0.11 and 0.59 ¡À 0.10, respectively, P > 0.05). However, it was markedly increased at day 5 (2.86 ¡À 0.37) and day 7 (3.19 ¡À 0.33) in the isograft group and was 1.57 ¡À 0.27 and 1.98 ¡À 0.13 in the allograft group at days 5 and 7, respectively. IFN-¦Ã protein and mRNA expression in the allograft group was increased at day 1 posttransplantation and reached a peak at day 3, and then it had a slight tendency of decline at day 5 and day 7. And they in the isograft group were at a low level at all times. The levels of ALR mRNA showed a negative correlation with levels of IFN-¦Ã mRNA in the allograft group (r = ?0.86, P < 0.05, y = ?0.241x + 0.586), whereas there is no correlation between ALR and IFN-¦Ã mRNA expression in the isograft group.

Conclusion

These data revealed an obviously negative correlation between ALR and IFN-¦Ã levels intragraft, which indicated that ALR may participate in immunoregulation of acute rejection.

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